This proposal centers about the mechanism of wound healing: control and assurance of collagen synthesis, angiogenesis and resistance to infection, and the respective roles of some important during fetal life. The first project is based on our observation that one of the most powerful means which clinicians possess to enhance early wound healing and resistance to infection lies in the control of oxygen delivery via blood perfusing the injured tissue. Specific impediments to oxygenation have been detected and will be measured, and strategies to overcome them are proposed for testing. These studies extend our past investigations, and we expect them to lead to simple, inexpensive clinical measures which are likely to enhance repair and prevent infection. The second project deals with the control of collagen synthesis via effects of the metabolic microenvironment of wound on collagen gene transcription and posttranslational modification. The vital role of lactate in wounds is being correlated with the initiation of control of collagen synthesis and response to hormonal, growth factor stimuli. The third project deals with the expression of a growth factor, somatomedin (IGF I), its binding protein and a similar factor, platelet-derived growth factor, in wound healing. Particular reference is paid to the normal production of IGF in wounds, the interaction of IGF and its binding protein, as well as local modifications of these substance which affect repair. The fourth project is an exploration of the scar process in fetal wounds, which are remarkable for their ability to heal without scar. Control of scar, collagen synthesis and protease production, with particular regard to the unusually hypoxic nature of fetal wounds, will be explored. The core laboratory provides models of wound healing, collection and processing of wound fluid specimens from patients and animals, and tissue and cell culture facilities, as well as facilities for measuring oxygen, selected growth factors, lactate, pH and inflammatory mediators.